Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans

Rennenberg, Roger J M W; Varik, Bernard J. van; Schurgers, Leon J.; Hamulyák, Karly; Cate, Hugo Ten; Leiner, Tim; Vermeer, Cees; Leeuw, Peter W. de; Kroon, Abraham A.

doi:10.1182/blood-2010-01-264598

Cited by 119 publications

(102 citation statements)

References 23 publications

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“…Arterial stiffness is influenced by the calcification of the elastic components of the artery wall, leading to hypertension. In humans, studies of limited sample size have reported an association of VKA treatment with calcification of the coronary arteries 8, 12, 13. Also, carotid intima‐media thickness is known to be correlated with atherosclerotic calcification 14.…”

Section: Discussionmentioning

confidence: 99%

“…The deficiency of active MGP and Gas‐6 provokes cell death, decreased contractility of vascular smooth muscle cells, and accelerated vascular calcification 4, 6. Studies have also demonstrated that VKA therapy is associated with vascular calcification 7, 8. Given the important role of vascular calcification in the pathophysiology of vascular stiffness and the correlation of calcification with increased serum levels of inflammatory markers, hypertension, and incident cardiovascular disease (CVD), VKA may exert clinically relevant noncoagulant effects 9…”

Section: Introductionmentioning

confidence: 99%

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Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population‐Based Gutenberg Health Study

Eggebrecht

Prochaska

Schulz

et al. 2018

JAHA

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BackgroundPreclinical data have indicated a link between use of vitamin K antagonists (VKA) and detrimental effects on vascular structure and function. The objective of the present study was to determine the relationship between VKA intake and different phenotypes of subclinical cardiovascular disease in the population.Methods and ResultsClinical and laboratory data, as well as medical–technical examinations were assessed from 15 010 individuals aged 35 to 74 years during a highly standardized 5‐hour visit at the study center of the population‐based Gutenberg Health Study. In total, the study sample comprised 287 VKA users and 14 564 VKA nonusers. Multivariable analysis revealed an independent association between VKA intake and stiffness index (β=+2.54 m/s; [0.41/4.66]; P=0.019), ankle‐brachial index (β=−0.03; [−0.04/−0.01]; P<0.0001), intima‐media thickness (β=+0.03 mm [0.01/0.05]; P=0.0098), left ventricular ejection fraction (β=−4.02% [−4.70/−3.33]; P<0.0001), E/E′ (β=+0.04 [0.01/0.08]; P=0.014) left ventricular mass (β=+5.34 g/m2.7 [4.26/6.44]; P<0.0001), and humoral markers of cardiac function and inflammation (midregional pro‐atrial natriuretic peptide: β=+0.58 pmol/L [0.50/0.65]; P<0.0001; midregional pro‐adrenomedullin: β=+0.18 nmol/L [0.14/0.22]; P<0.0001; N‐terminal pro B‐type natriuretic peptide: β=+1.90 pg/mL [1.63/2.17]; P<0.0001; fibrinogen: β=+143 mg/dL [132/153]; P<0.0001; C‐reactive protein: β=+0.31 mg/L [0.20/0.43]; P<0.0001). Sensitivity analysis in the subsample of participants with atrial fibrillation stratified by intake of VKA demonstrated consistent and robust results. Genetic variants in CYP2C9,CYP4F2, and VKORC1 were modulating effects of VKA on subclinical markers of cardiovascular disease.ConclusionsThese data demonstrate negative effects of VKA on vascular and cardiac phenotypes of subclinical cardiovascular disease, indicating a possible influence on long‐term disease development. These findings may be clinically relevant for the provision of individually tailored antithrombotic therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population‐Based Gutenberg Health Study

Eggebrecht

Prochaska

Schulz

et al. 2018

JAHA

Self Cite

View full text Add to dashboard Cite

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“…Crosssectional studies indicate an association between anticoagulant therapy with Coumadin (warfarin) and calcium phosphate deposition in arterial tunica media (3,4). In rodents, warfarin treatment induces rapid VC and decreased arterial compliance (5,6) akin to elastocalcinosis, a condition prevalent in the elderly population and characterized by calcium deposition along the elastic lamellae.…”

Section: Vascular Calcification (Vc)mentioning

confidence: 99%

Quercetin Attenuates Warfarin-induced Vascular Calcification in Vitro Independently from Matrix Gla Protein

Beazley

Eghtesad

Nurminskaya

2013

Journal of Biological Chemistry

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Background: Molecular mechanism(s) of warfarin-induced vascular calcification are not well known. Results: Inhibition of ␤-catenin signaling with shRNA or quercetin prevents osteoblastic transformation and calcification in VSMCs and calcification in aortic rings treated with warfarin, independent from MGP and protein carboxylation. Conclusion: Quercetin inhibits vascular calcification via ␤-catenin signaling. Significance: Quercetin may be instrumental in treatment of warfarin-induced vascular calcification.

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“…The long-term use of oral anticoagulants (warfarin and coumarin) should be avoided. Long-term use of those agents increases the likelihood of VC [154,155]. Once the patient proceeds to CKD G5, pre-emptive kidney transplantation is the best option to improve patient and graft survival in comparison to patients admitted to dialysis or to patients transplanted after starting dialysis.…”

Section: Resultsmentioning

confidence: 99%

Arterial Calcification in Chronic Kidney Disease: Whom? When? and How to Handle?

2016

J Urol Nephrol

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Chronic kidney disease (CKD) patients have the highest mortality rate compared to other chronic diseases. Cardiovascular events account for up to 60% of the mortalities, with cardiovascular calcifications affecting the majority of those CKD patients. Most of this calcification is related to disturbed renal phosphate handling. Fibroblast growth factor 23 (FGF23) and Klotho were incriminated in the pathogenesis of vascular calcification (VC) through different mechanisms including their effect on endothelium and arterial wall smooth muscle cells. In addition, deficient Klotho gene expression is a constant feature in CKD patients. This deficiency, not only promotes vascular pathology, but also has a role in the progression of the CKD. This review will cover the medical history, prevalence, pathogenesis, clinical relevance, diagnostic tools, the ideal timing to prevent or to withhold the progression of VC and the different medications and medical procedures that can help to prolong the survival of CKD patients. IntroductionThe problematic increase of cardiovascular morbidity and mortality is behind the increased interest in VC among CKD patients. VC is a strong predictor of increased cardiovascular mortality among CKD patients. However, almost all of the clinical studies that have tried to manipulate the various risk factors for VC in dialysis patients have failed to show a significant impact on patient survival. On the other hand, when pre-dialysis patients underwent similar studies, there was a significant decrease in cardiovascular and overall mortality rates, as well as a comparable effect on VC progress rate. These results point toward the importance of early intervention. The ideal timing and dynamics of this intervention will be thoroughly discussed. VC In CKD PatientsThe prevalence of VC among pre-dialysis CKD G3-5 patients is 79% as reported in a recent study [1]. It might approach 100% in patients starting dialysis [2]. Upto 3-4 fold increase in VC has been reported in the earliest phases of CKD [3].VC in CKD can affect the tunica intima and/or the tunica media layers. Intimal calcification is mainly a feature of atherosclerosis [4]. Medial calcification is restricted to CKD and is encountered even at young ages [5,6]. Hemodialysis (HD) patients have higher calcification scores than both peritoneal dialysis (PD) and CKD G4 patients. More heavily calcified patients were significantly older and mostly male [7]. In HD patients, coronary calcification progresses steadily [8]. High serum phosphate concentration was a strong independent risk factor only in non-diabetic patients. Diabetic patients lack similar associations [9]. Patients starting dialysis at the age of 25-29 years have an expected survival 33 years less than the general populous. Arterial calcification is one of the predictors of this increased cardiovascular mortality [10].The prevalence of coronary artery calcification (CAC) in kidney transplant recipients (KTRs) is higher (61-75%) than that assessed in CKD G3, [11,12] and lower than tha...

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Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans

Cited by 119 publications

References 23 publications

Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population‐Based Gutenberg Health Study

Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population‐Based Gutenberg Health Study

Quercetin Attenuates Warfarin-induced Vascular Calcification in Vitro Independently from Matrix Gla Protein

Arterial Calcification in Chronic Kidney Disease: Whom? When? and How to Handle?

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